Co-evolution of ligand-receptor pairs in the vasopressin/oxytocin superfamily of bioactive peptides.

R.E. van Kesteren, C.P. Tensen, A.B. Smit, J. van Minnen, L.F. Kolakowski, W. Meyerhof, D. Richter, H. van Heerikhuizen, E. Vreugdenhil, W.P.M. Geraerts

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In order to understand the molecular mechanisms that underlie the co- evolution of related yet functionally distinct peptide-receptor pairs, we study receptors for the vasopressin-related peptide Lys-conopressin in the mollusc Lymnaea stagnalis. In addition to a previously cloned Lys-conopressin receptor (LSCPR1), we have now identified a novel Lys-conopressin receptor subtype, named LSCPR2. The two receptors have a differential distribution in the reproductive organs and the brain, which suggests that they are involved in the control of distinct aspects of reproduction and mediate transmitter- like and/or modulatory effects of Lys-conopressin on different types of central neurons. In contrast to LSCPR1, LSCPR2 is maximally activated by both Lys-conopressin and Ile-conopressin, an oxytocin-like synthetic analog of Lys-conopressin. Together with a study of the phylogenetic relationships of Lys-conopressin receptors and their vertebrate counterparts, these data suggest that LSCPR2 represents an ancestral receptor to the vasopressin/oxytocin receptor family in the vertebrates. Based on our findings, we provide a theory of the molecular co-evolution of the functionally distinct ligand-receptor pairs of the vasopressin/oxytocin superfamily of bioactive peptides.
Original languageEnglish
Pages (from-to)3619-3626
JournalJournal of Biological Chemistry
Publication statusPublished - 1996


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